3Amyotrophic Lateral Sclerosis Progressive, degenerative neurologic disease of unknown etiologyInvolves both upper and lower motor neuronsLMN: weakness, atrophy, fasiculation due to denervation of muscles – amyotrophicUMN: hyperreflexia, spasticity due to lateral corticospinal tract degeneration – lateral sclerosis
4ALS continuedMuscle atrophy and spasticity in limb and bulbar muscles result in weakness and loss of ambulation, oropharyngeal dysfunction, weight loss, and ultimately respiratory failure.The mainstay of treatment for ALS patients is still palliative and symptomatic management.It is important to provide anticipatory guidance, and continue the discussion of goals of care.
5Pathology & Etiology Motor neuron degeneration and death Superoxide dismutase type 1 mediated toxicityExcitotoxicity via glutamate mediated signalingCytoskeletal derangements, mitochondrial dysfunction, viral infections, apoptosis
6Epidemiology & Prognosis 5000 new case in the U.S. per year90% cases sporadic, 10% familialIncidence 1.47~2.7 per 100,000 per yearPrevalence 2.7~7.4 per 100,000 per year70% die within 3~5 years of diagnosis10~20% survive for more than 10 yearsImproved survival associated with younger age of onset, male gender and limb rather than bulbar symptoms
7RiluzoleRiluzole reduces the presynaptic release of glutamate, but the precise mechanism of action in ALS is unclear. It is postulated that it may be neuroprotective by reducing excitotoxicity that is due to excess glutamate, and it may also act as a glutamate receptor antagonist.
8Riluzole continuedClinical trials so far do show that Riluzole improved survival, especially in younger populations, but demonstrated no beneficial effect on bulbar function or muscle strengthThe pts who are most likely to benefit are those who have symptoms for less than 5 years, vital capacity >60%, and no tracheostomy. 50mg PO BID.The implication here based on best available data is that pt with end stage or advanced disease do not seem to benefit from Riluzole. Therefore starting the medication late in the course of the illness or even continuation of the medication in a hospice setting is not warranted.
9Signs & Symptoms Limb spasticity Hyperreflexia Brisk jaw reflex Babinski's signPseudobulbar palsy with emotional labilityFocal or multifocal limb weakness & atrophyCramps & fasciculationsDysarthria, dysphagia and/or chokingTongue atrophy with fasciculationsClaw handFatigueDyspnea
10Secretion managementIn ALS there is overall decreased saliva production, sialorrhea is more a poor handling of saliva.The management is similar for pts with cerebral palsy, MR, oropharyngeal carcinoma, Down syndrome.Decrease saliva production, or divert and remove saliva
11Secretion management Glycopyrrolate (Robinul) 1~2mg BID or TID Benztropine (Cogentin) 0.5~2.0mg QD or BID or Atropine 0.4mg Q4~6 hoursAmitriptyline (Elavil) 10~150mg QHSTransdermal scopolamine one or two patches every three daysTrihexyphenidyl (Artane) 1 to 2 mg per day slowly increasing to total of 5 to 15 mg daily in three or four divided dosesMay also try Clonidine, LevsinMuch data is derived from studies in other neurologic diseases
12Secretion managementBotulinum toxin injection into the salivary glands appears to be safe and useful in preliminary studiesExternal beam radiation [3-30 Gy; 3-10 fractions]Surgical interventions have been tried w/o demonstrated efficacy
16Muscle spasm & weakness Early PT/OT involvementVariety of assist devices may provide, mobility, support, comfort and increase functionality, i.e. braces, wheelchair, special air beds, head rests, etc.
17Muscle spasm & weakness CrampsQuinine sulfate 200 mg twice a dayTizanidine 2 to 4 mg by mouth twice daily up to a total dose of 24 mg dailyCarbamazepine 200 mg twice dailyPhenytoin 100 mg once to three times a dayFor mild symptoms:Magnesium 5 mmol once to three times a dayVitamin E 400 IE twice a day
18Muscle spasm & weakness SpasticityBaclofen 5 to 10 mg twice daily to three times dailyTizanidine 2 to 4 mg by mouth twice daily up to a total dose of 24 mg dailyMemantine starting at 5 mg daily, increasing by 5 mg a week to a maximum of 20 mg twice a dayTetrazepam 50 mg at bedtime, increasing by 25 mg a day to a maximum dose of 150 mg taken two to three times a day
19Pseudobulbar affectAlso known as: pseudobulbar palsy, emotional incontinence, pathologic crying/laughingThe emotional lability is NOT a mood disorder, but is an uncontrolled outburst and is a very troubling symptom for patients.It is an abnormal affective display that can be seen in about 50% of ALS patients.
20Pseudobulbar affect Amitriptyline 10~150mg QHS Fluvoxamine (Luvox) 100~200mg QDAlternatively may try Lithium or L-Dopa
21ConstipationCommon symptom due to immobility and side effects from opioid, anti-cholinergics, muscle relaxants
22PainOften results from muscle contracture, joint stiffness, and immobility leading to pressure ulcers at later stage of disease
23Sleep problems Often associated with other symptoms Identify and treat underlying causesUse sedative cautiously
24Dysarthria Speech therapy often helpful early Computer technology offer many options to assist with patient communication
25Dysphagia and nutrition Decreased caloric and fluid intake may lead to worsening of symptoms, such as weakness, muscle atrophy, fatigueInitially management includes the modification of food and liquid consistencyDiscussion of possible PEG placement
26Dysphagia and nutrition For optimal safety and efficacy, PEG placement should be performed before the forced vital capacity falls to below 50% of predicted and not in the preterminal phase.The indications should be to evaluate for symptoms of hunger, choking, sign of inadequate oral intake, and diminished quality of life, rather than a swallow evaluation.
27Dysphagia and nutrition Complications for PEG include:Transient laryngeal spasm 7.2%Localized infection 6.6Gastric hemorrhage 1~4%Death 1.9%Does NOT prevent aspiration pneumoniaStudies suggest that with PEG survival is prolonged by 1~4 months
29Respiratory careIt is important to initiate discussion regarding the patient’s goals and how those goal can be best achieved with respect to respiratory care including non-invasive and invasive mechanical ventilation.Respect the right of patients to refuse or withdraw treatment.
30Respiratory careA decrease of VC to <50% is often associated with respiratory symptoms.A VC of less than 1L or 25~30% of predicted is associated with significant risk of respiratory failure and sudden death.There are no current guidelines on how frequently to test VC.
31Respiratory care Dyspnea Oxygen can be administered for hypoxia Body position such as elevation is often helpfulChest physiotherapy in the early phaseOpioid can be used to treat dyspnea and benzodiazepines for associated anxietyInhaled opioids have not consistently demonstrated benefit; inhaled lidocaine appears to be more efficaciousOxygen can be administered for hypoxia
32Respiratory careMonths to years before terminal respiratory failure, symptoms of chronic nocturnal hypoventilation frequently presents and impair the patient’s quality of life.The symptoms include: daytime fatigue, concentration difficulty, headache, disturbed sleep, nightmares, nervousness, depression, anxiety, tachypnea, tachycardia, diaphoresis, dyspnea, phonation difficulties, reduced appetite, weight loss, gastritis, cyanosis, edema, recurrent URI, dizziness, syncope, visual disturbance, diffuse pain
33Respiratory careNon-invasive intermittent ventilation administered at night for 4 hours is an efficient way of alleviating nocturnal symptoms.It should be made clear that this effort is for the purpose of symptom management and improving the quality of life rather than prolongation.
34Respiratory careIt is important to explore other means of ventilatory support should it be desired. The goals of such support and when to discontinue such therapies when the goals are no longer being met. Patients need to be reassured that all necessary care will be provided to ensure their comfort.Non-invasive: Negative pressure body ventilators and oscillators, Intermittent abdominal pressure ventilator, Intermittent positive pressure ventilators (mouth/nasal)Tracheostomy & ventilation
35Respiratory care Patients show higher satisfaction with NIV than IV. Studies show that ventilator dependent patients are not more depressed than patients who are not vent dependent, and can lead meaningful lives.But there is greater financial, social and emotional burden.Note self-selection bias
36Respiratory care AAN Practice Parameter Why do we disagree with this particular algorithm!
37Other symptoms Urinary frequency/urgency Peripheral edema Laryngospasm In the absence of UTI, often due to spasticity that responds well to OxybutininPeripheral edemaOften dependent: elevation, massage, compression hose (r/o DVT)LaryngospasmSudden reflex closure of vocal cords due to variety of stimuli, usually resolves spontaneouslyH1 and H2 blocking agents may be helpful
38Psychosocial and spiritual care The role of continued support for patient and family cannot be underestimated or overstated.Bereavement and grief counseling from diagnosis
39Additional resources ALS Association (www.alsa.org) Muscular Dystrophy Association (www.mdausa.org)Links to resources for patients and familiesBooks:Learning to Fall: The Blessings of an Imperfect Life, Philip SimmonsTuesdays with Morrie, Mitch AlbomThere are many these are some of my personal favorites
40Special considerations in pediatrics using SMA (spinal muscular atrophy) as a model